Despite the recent advances in the treatment of ischemic heart disease, there still exist a significant number of patients for whom conventional therapies such as angioplasty and coronary bypass surgery are not feasible options. In particular, alternative therapies are required for patients in a number of circumstances. For example, patients with diffuse small vessel coronary artery disease cannot be treated by conventional coronary bypass surgery because of the small size and large number of diseased vessel segments. In other patients, re-occlusion of a diseased vessel may occur despite multiple angioplastic procedures or bypass surgeries. Accordingly, the need exists for alternative intervention methods.
One promising alternative treatment for ischemic heart disease is the delivery of angiogenesis-promoting substances to the heart tissue to induce angiogenesis. Angiogenesis is a complex biological process that results in the growth of new blood vessels within tissue. Angiogenesis is an essential process common to several normal and pathologic conditions including embryologic development, wound healing, development of neoplasms, and the like.
Angiogenesis has also been induced in heart tissue for re-perfusion of tissue compromised by myocardial ischemia. Several growth factors have been identified and are intimately involved in initiating and promoting angiogenesis in tissue within a living body. These growth factors are typically proteins which stimulate endothelial cell reproduction in the target tissue. The tissue must be exposed to the growth factors for a period of time, i.e., a number of days. In addition, the growth factor should be limited to the target tissue so that angiogenesis is not induced in sensitive non-diseased organs, such as the retina, or in occult tumors.
The growth factor may be delivered to the target tissue through the use of indwelling catheters over a period of time. However, a preferred method of delivering the growth factor is in the form of gene transfer by a replication deficient adenoviral vector. Under this method, a quantity of adenovirus having the desired genetic component is delivered to the treatment area by injection in solution.
In the past, an open-chest procedure has been used to deliver the treatment solution. According to this procedure, the patient's chest is opened surgically to expose the heart. The solution containing the adenovirus is then delivered to the heart tissue by using a syringe to make a number of injections in a grid-like pattern, with the surgeon keeping track of the location of each injection. Once injected, the adenovirus causes the cells in the target tissue to express the desired growth factor protein, and this protein expression from the treated cells will continue for the desired period of time. Previous studies have shown the feasibility and efficacy of safe, sustained, and localized expression of angiogenesis-promoting growth factors utilizing adenoviral-mediated gene transfer therapy.
It is desirable, however, to be able to provide the above-described therapy without the necessity of performing open-chest surgery on the patient. Accordingly, the present invention sets forth an apparatus and method for providing gene therapy treatment to the heart or other internal organs in a minimally invasive manner. The present invention also provides an apparatus and method for delivering angiogenesis-promoting substances to an area of diseased tissue with greater ease and efficiency, and with reduced trauma and recovery time for the patient. Accordingly, the subject invention could be potentially helpful to hundreds of thousands of patients with severe ischemic heart disease who are not candidates for surgical bypass or balloon angioplasty.